&p.1:Abstract Hair follicles are complex organs of the skin, in morphological and ontogenic continuity with the epi- dermis. We have examined the location of desmosomal cadherins and desmosomal plaque proteins in the hair follicle of adult and fetal human scalp skin by immuno- histochemistry and have established a localization “map” of the hair follicle. Using antibodies against the plaque proteins desmoplakin I and II, plakoglobin, and plako- philin 1, we have found that these occur in most, if not all hair follicle desmosomes, whereas plakophilin 2 was absent, except in the basal cells of the outer root sheath, where a weak reactivity was found. By contrast, the desmosomal cadherins were mostly differentially synthe- sized, displaying a complicated map. While desmocollin Dsc3 was detected in all cell types examined, Dsc1 was detected only in the outer root sheath companion cell layer and the inner root sheath, and Dsc2 showed practi- cally a mutually exclusive presence. Desmoglein Dsg2 was observed in basal cells of the outer root sheath as well as in the central cell layers of the subinfundibular outer rood sheath, matrix cells and trichocytes, in partial overlap with the otherwise different immunopositive re- actions of Dsg1 and Dsg3. We have also determined when these proteins are synthesized during fetal hair fol- licle development. The differential molecular composi- tion of desmosomes is discussed in relation to possible functional differences between the individual cell types.&bdy: Introduction Desmosomes are morphologically and compositionally defined intercellular adhering junctions which represent hallmarks of epithelial differentiation but also occur in the myocardiac intercalated disks and the Purkinje fibers of the heart, between arachnoidal cells of leptomeninges, and in the dendritic reticulum of lymph node follicles [11, 12, 15, 16, 20, 43, 61]. Analytical studies using cell fractionation, cDNA cloning techniques, immunoblotting and immunolocalization experiments have allowed us to determine the major constituents of desmosomes. Desmogleins and desmocollins are the main desmoso- mal transmembrane proteins. They belong to the family of Ca 2+ -dependent cell adhesion molecules (“cadherins”) and show structural homologies with the classical E- and P-cadherins. At present, three different isoforms of both desmogleins and desmocollins, termed Dsg1–3 and Dsc1–3, have been distinguished [1, 6, 7, 9, 20, 29, 30, 32–36, 39, 45, 54–56, 64, 66]. Their cytoplasmic por- tions are associated with a distinct set of plaque proteins, including common ones such as desmoplakin I and plakoglobin, and cell type-specific ones such as des- moplakin II and plakophilins 1, 2 or 3 [3, 11, 12, 22, 26, 28, 40, 59, 60]. In the human epidermis, desmoplakins I and II, plakoglobin and plakophilin 1 are most promi- nent, with vertically increasing abundance. The genes encoding desmosomal cadherins also show differentiation-specific expression in the human epider- mis. Dsg1 is synthesized exclusively in the suprabasal layers, Dsg2 in varying abundance in the basal layers of certain types of epidermis, and Dsg3 in both the basal and the lower suprabasal compartments. Similarly, Dsc1 H. Kurzen · S. Schäfer · W.W. Franke ( ✉ ) Division of Cell Biology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany H. Kurzen · I. Moll Department of Dermatology, University of Hamburg, Hamburg, Germany R. Moll Department of Pathology, Philipps University, 35033 Marburg, Germany E. Simics Department of Dermatology, Mannheim Medical School, University of Heidelberg, Mannheim, Germany and Department of Dermatology, University Medical School, Debrecen, Hungary M. Amagai Department of Dermatology, Keio University School of Medicine, Tokyo, Japan M.J. Wheelock Department of Biology, University of Toledo, Toledo, Ohio 43606-3390, USA&/fn-block: Differentiation (1998) 63:295–304 © Springer-Verlag 1998 ORIGINAL ARTICLE &roles:Hjalmar Kurzen · Ingrid Moll · Roland Moll Stephan Schäfer · Enikö Simics · Masayuki Amagai Margaret J. Wheelock · Werner W. Franke Compositionally different desmosomes in the various compartments of the human hair follicle Accepted in revised form: 24 June 1998